Photoinduced, Copper-Catalyzed Alkylation of Amines: A Mechanistic Study of the Cross-Coupling of Carbazole with Alkyl Bromides
Abstract
We have recently reported that a variety of couplings of nitrogen, sulfur, oxygen, and carbon nucleophiles with organic halides can be achieved under mild conditions (−40 to 30 °C) through the use of light and a copper catalyst. Insight into the various mechanisms by which these reactions proceed may enhance our understanding of chemical reactivity and facilitate the development of new methods. In this report, we apply an array of tools (EPR, NMR, transient absorption, and UV–vis spectroscopy; ESI–MS; X-ray crystallography; DFT calculations; reactivity, stereochemical, and product studies) to investigate the photoinduced, copper-catalyzed coupling of carbazole with alkyl bromides. Our observations are consistent with pathways wherein both an excited state of the copper(I) carbazolide complex ([Cu^I(carb)_2]^−) and an excited state of the nucleophile (Li(carb)) can serve as photoreductants of the alkyl bromide. The catalytically dominant pathway proceeds from the excited state of Li(carb), generating a carbazyl radical and an alkyl radical. The cross-coupling of these radicals is catalyzed by copper via an out-of-cage mechanism in which [Cu^I(carb)_2]^− and [Cu^(II)(carb)_3]^− (carb = carbazolide), both of which have been identified under coupling conditions, are key intermediates, and [Cu^(II)(carb)_3]^− serves as the persistent radical that is responsible for predominant cross-coupling. This study underscores the versatility of copper(II) complexes in engaging with radical intermediates that are generated by disparate pathways, en route to targeted bond constructions.
Additional Information
© 2017 American Chemical Society. Received: July 6, 2017; Published: August 17, 2017. Support has been provided by the National Institutes of Health (National Institute of General Medical Sciences: R01–109194), the Natural Sciences and Engineering Research Council of Canada (graduate research fellowship for J.M.A.), and the National Science Foundation (support of the Caltech EPR Facility (NSF-1531940) and a graduate research fellowship for T.S.R.). Additional support has been provided by the Arnold and Mabel Beckman Foundation through the Caltech Beckman Institute Laser Resource Center. We thank Dr. Angel J. Di Bilio, Dr. Paul Oyala, Dr. Sidney E. Creutz, Lawrence M. Henling, Dr. Marcin Kalek, Dr. Wesley Sattler, Dr. Oliver S. Shafaat, Dr. Mona Shahgholi, Dr. David VanderVelde, and Dr. Jay R. Winkler for technical assistance and helpful discussions. The authors declare no competing financial interest.Attached Files
Accepted Version - nihms917166.pdf
Supplemental Material - ja7b07052_si_001.pdf
Supplemental Material - ja7b07052_si_002.cif
Supplemental Material - ja7b07052_si_003.mol
Files
Additional details
- PMCID
- PMC5685493
- Eprint ID
- 80616
- DOI
- 10.1021/jacs.7b07052
- Resolver ID
- CaltechAUTHORS:20170818-105931485
- NIH
- R01-109194
- Natural Sciences and Engineering Research Council of Canada (NSERC)
- NSF
- CHE-1531940
- NSF Graduate Research Fellowship
- Arnold and Mabel Beckman Foundation
- Created
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2017-08-18Created from EPrint's datestamp field
- Updated
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2021-11-15Created from EPrint's last_modified field